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BACKGROUND: Tea pests pose a significant threat to tea leaf yield and quality, necessitating fast and accurate detection methods to improve pest control efficiency and reduce economic losses for tea farmers. However, in real tea gardens, some tea pests are small in size and easily camouflaged by complex backgrounds, making it challenging for farmers to promptly and accurately identify them. RESULTS: To address this issue, we propose a real-time detection method based on TP-YOLOX for monitoring tea pests in complex backgrounds. Our approach incorporates the CSBLayer module, which combines convolution and multi-head self-attention mechanisms, to capture global contextual information from images and expand the network's perception field. Additionally, we integrate an efficient multi-scale attention module to enhance the model's ability to perceive fine details in small targets. To expedite model convergence and improve the precision of target localization, we employ the SIOU loss function as the bounding box regression function. Experimental results demonstrate that TP-YOLOX achieves a significant performance improvement with a relatively small additional computational cost (0.98 floating-point operations), resulting in a 4.50% increase in mean average precision (mAP) compared to the original YOLOX-s. When compared with existing object detection algorithms, TP-YOLOX outperforms them in terms of mAP performance. Moreover, the proposed method achieves a frame rate of 82.66 frames per second, meeting real-time requirements. CONCLUSION: TP-YOLOX emerges as a proficient solution, capable of accurately and swiftly identifying tea pests amidst the complex backgrounds of tea gardens. This contribution not only offers valuable insights for tea pest monitoring but also serves as a reference for achieving precise pest control. © 2023 Society of Chemical Industry.
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Algoritmos , Árboles , Humanos , Agricultores , Jardinería , TéRESUMEN
Fluorescent imaging of biological systems in the second near-infrared window (NIR-II) can probe tissue at centimetre depths and achieve micrometre-scale resolution at depths of millimetres. Unfortunately, all current NIR-II fluorophores are excreted slowly and are largely retained within the reticuloendothelial system, making clinical translation nearly impossible. Here, we report a rapidly excreted NIR-II fluorophore (â¼90% excreted through the kidneys within 24 h) based on a synthetic 970-Da organic molecule (CH1055). The fluorophore outperformed indocyanine green (ICG)-a clinically approved NIR-I dye-in resolving mouse lymphatic vasculature and sentinel lymphatic mapping near a tumour. High levels of uptake of PEGylated-CH1055 dye were observed in brain tumours in mice, suggesting that the dye was detected at a depth of â¼4 mm. The CH1055 dye also allowed targeted molecular imaging of tumours in vivo when conjugated with anti-EGFR Affibody. Moreover, a superior tumour-to-background signal ratio allowed precise image-guided tumour-removal surgery.
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Benzopiranos/farmacología , Carcinoma de Células Escamosas/patología , Colorantes Fluorescentes/farmacología , Indoles/farmacología , Neoplasias Experimentales/patología , Fenilpropionatos/farmacología , Tiadiazoles/farmacología , Animales , Benzopiranos/química , Benzopiranos/orina , Línea Celular Tumoral , Diagnóstico por Imagen/métodos , Femenino , Humanos , Indoles/química , Indoles/orina , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Espectroscopía Infrarroja CortaRESUMEN
Dozens of observational studies and two meta-analyses have investigated the association of migraine with the risk of stroke, but their results are inconsistent. We aimed to quantitatively evaluate the relationship between migraine and stroke risk by performing a meta-analysis of prospective cohort studies. PubMed and Embase were searched through July 2016 to identify studies that met pre-stated inclusion criterion and reference lists of retrieved articles were also reviewed. Information on the characteristics of the included study, risk estimates, and control for possible confounding factors were extracted independently by two authors. The random-effects model was used to calculate the pooled risk estimates. Eleven prospective cohort studies involving 3371 patients with stroke and 2,221,888 participants were included in this systematic review. Compared with non-migraineurs, the pooled relative risks of total stroke, hemorrhagic stroke, and ischemic stroke for migraineurs were 1.55 [95% confidence interval (CI) 1.38-1.75], 1.15 (95% CI 0.85-1.56), and 1.64 (95% CI 1.22-2.20), respectively. Exception of any single study did not materially alter the combined risk estimate. Integrated epidemiological evidence supports that migraine should be associated with the increased risk of total stroke and ischemic stroke, but the relationship between migraine and the risk of hemorrhagic stroke is not of certainty.
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Trastornos Migrañosos/epidemiología , Accidente Cerebrovascular/epidemiología , Humanos , Incidencia , RiesgoRESUMEN
Alginate/chitosan nanocomposite particles (GSNO-acNCPs), i.e. S-nitrosoglutathione (GSNO) loaded polymeric nanoparticles incorporated into an alginate and chitosan matrix, were developed to increase the effective GSNO loading capacity, a nitric oxide (NO) donor, and to sustain its release from the intestine following oral administration. Compared with free GSNO and GSNO loaded nanoparticles, GSNO-acNCPs promoted 2.7-fold GSNO permeation through a model of intestinal barrier (Caco-2 cells). After oral administration to Wistar rats, GSNO-acNCPs promoted NO storage into the aorta during at least 17h, as highlighted by (i) a long-lasting hyporeactivity to phenylephrine (decrease in maximum vasoconstrictive effect of aortic rings) and (ii) N-acetylcysteine (a thiol which can displace NO from tissues)-induced vasodilation of aorxxtic rings preconstricted with phenylephrine. In conclusion, GSNO-acNCPs enhance GSNO intestinal absorption and promote the formation of releasable NO stores into the rat aorta. GSNO-acNCPs are promising carriers for chronic oral application devoted to the treatment of cardiovascular diseases.
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Nanocompuestos , Óxido Nítrico/metabolismo , Polímeros , S-Nitrosoglutatión/farmacocinética , Animales , Aorta , Células CACO-2 , Humanos , Absorción Intestinal , Ratas , Ratas WistarRESUMEN
Due to overexpression of glycyrrhetinic acid (GA) receptor in liver cancer cells, glycyrrhetinic acid modified recombinant human serum albumin (rHSA) nanoparticles for targeting liver tumor cells may result in increased therapeutic efficacy and decreased adverse effects of cancer therapy. In this study, doxorubicin (DOX) loaded and glycyrrhetinic acid modified recombinant human serum albumin nanoparticles (DOX/GA-rHSA NPs) were prepared for targeting therapy for liver cancer. GA was covalently coupled to recombinant human serum albumin nanoparticles, which could efficiently deliver DOX into liver cancer cells. The resultant GA-rHSA NPs exhibited uniform spherical shape and high stability in plasma with fixed negative charge (â¼-25 mV) and a size about 170 nm. DOX was loaded into GA-rHSA NPs with a maximal encapsulation efficiency of 75.8%. Moreover, the targeted NPs (DOX/GA-rHSA NPs) showed increased cytotoxic activity in liver tumor cells compared to the nontargeted NPs (DOX/rHSA NPs, DOX loaded recombinant human serum albumin nanoparticles without GA conjugating). The targeted NPs exhibited higher cellular uptake in a GA receptor-positive liver cancer cell line than nontargeted NPs as measured by both flow cytometry and confocal laser scanning microscopy. Biodistribution experiments showed that DOX/GA-rHSA NPs exhibited a much higher level of tumor accumulation than nontargeted NPs at 1 h after injection in hepatoma-bearing Balb/c mice. Therefore, the DOX/GA-rHSA NPs could be considered as an efficient nanoplatform for targeting drug delivery system for liver cancer.
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Antineoplásicos/administración & dosificación , Doxorrubicina/administración & dosificación , Neoplasias Hepáticas Experimentales/tratamiento farmacológico , Nanocápsulas/química , Animales , Antineoplásicos/farmacocinética , Doxorrubicina/farmacocinética , Sistemas de Liberación de Medicamentos , Ácido Glicirretínico/química , Células HeLa , Células Hep G2 , Humanos , Neoplasias Hepáticas Experimentales/metabolismo , Espectroscopía de Resonancia Magnética , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Microscopía Electrónica de Transmisión , Nanocápsulas/administración & dosificación , Nanocápsulas/ultraestructura , Proteínas Recombinantes/química , Albúmina Sérica/química , Distribución Tisular , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
BACKGROUND: Few studies on cluster-based synthetic effects of multiple risk factors for birth defects have been reported. The present study aimed to identify maternal exposure clusters, explore the association between clusters of risk factors and birth defects, and further screen women with high risk for birth defects among expectant mothers. METHODS: Data were drawn from a large-scale, retrospective epidemiological survey of birth defects from 2006 to 2008 in six counties of Shanxi Province, China, using a three-level stratified random cluster sampling technique. Overall risk factors were extracted using eight synthetic variables summed and examined as a total risk factor score: maternal delivery age, genetic factors, medical history, nutrition and folic acid deficiency, maternal illness in pregnancy, drug use in pregnancy, environmental risk factors in pregnancy, and unhealthy maternal lifestyle in pregnancy. Latent class cluster analysis was used to identify maternal exposure clusters based on these synthetic variables. Adjusted odds ratios (AOR) were used to explore associations between clusters and birth defects, after adjusting for confounding variables using logistic regression. RESULTS: Three latent maternal exposure clusters were identified: a high-risk (6.15%), a moderate-risk (22.39%), and a low-risk (71.46%) cluster. The prevalence of birth defects was 14.08%, 0.85%, and 0.52% for the high-, middle- and low-risk clusters respectively. After adjusting for maternal demographic variables, women in the high-risk cluster were nearly 31 times (AOR: 30.61, 95% CI: [24.87, 37.67]) more likely to have an infant with birth defects than low-risk women. CONCLUSIONS: A high-risk group of mothers in an area with a high risk for birth defects were screened in our study. Targeted interventions should be conducted with women of reproductive age to improve neonatal birth outcomes in areas with a high risk of birth defects.
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Anomalías Congénitas/epidemiología , Anomalías Congénitas/etiología , Deficiencia de Ácido Fólico , Edad Materna , Exposición Materna , Complicaciones del Embarazo , Adulto , China , Análisis por Conglomerados , Femenino , Humanos , Lactante , Estilo de Vida , Modelos Logísticos , Tamizaje Masivo , Oportunidad Relativa , Embarazo , Estudios Retrospectivos , Factores de RiesgoRESUMEN
A novel series of benzenesulfonamide derivatives containing 4-aminobenzenesul-fonamide and α-amides branched valproic acid or 2,2-dimethylcyclopropanecarboxylic acid moieties were synthesized and screened for their anticonvulsant activities in mice maximal electroshock seizure (MES) and subcutaneous pentylenetetrazole (scPTZ) test. The activity experimental study showed that 2,2-dipropyl-N¹-(4-sulfamoylphenyl)malonamide (18b) had the lowest median effective dose (ED50) of 16.36 mg/kg in MES test, and 2,2-dimethyl-N-(4-sulfamoylphenyl)cyclopropane-1,1-dicarboxamide (12c) had the lowest ED50 of 22.50 mg/kg in scPTZ test, which resulted in the protective indexe (PI) of 24.8 and 20.4, respectively. These promising data suggest the new compounds have good potential as new class of anticonvulsant agents with high effectiveness and low toxicity for the treatment of epilepsy.
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Anticonvulsivantes/síntesis química , Convulsiones/tratamiento farmacológico , Sulfonamidas/síntesis química , Animales , Anticonvulsivantes/administración & dosificación , Anticonvulsivantes/química , Modelos Animales de Enfermedad , Masculino , Ratones , Estructura Molecular , Convulsiones/etiología , Relación Estructura-Actividad , Sulfonamidas/administración & dosificación , Sulfonamidas/química , BencenosulfonamidasRESUMEN
Small-molecule-based multimodal and multifunctional imaging probes play prominent roles in biomedical research and have high clinical translation ability. A novel multimodal imaging platform using base-catalyzed double addition of thiols to a strained internal alkyne such as bicyclo[6.1.0]nonyne has been established in this study, thus allowing highly selective assembly of various functional units in a protecting-group-free manner. Using this molecular platform, novel dual-modality (PET and NIRF) uPAR-targeted imaging probe: (64)Cu-CHS1 was prepared and evaluated in U87MG cells and tumor-bearing mice models. The excellent PET/NIRF imaging characteristics such as good tumor uptake (3.69%ID/g at 2â h post-injection), high tumor contrast, and specificity were achieved in the small-animal models. These attractive imaging properties make (64)Cu-CHS1 a promising probe for clinical use.
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Alquinos/química , Ciclooctanos/química , Imagen Molecular , Sondas Moleculares/química , Neoplasias Experimentales/diagnóstico , Alquinos/farmacocinética , Animales , Línea Celular Tumoral , Ciclooctanos/farmacocinética , Modelos Animales de Enfermedad , Humanos , Ratones , Sondas Moleculares/farmacocinética , Estructura Molecular , Tomografía de Emisión de Positrones , Compuestos de Sulfhidrilo/química , Compuestos de Sulfhidrilo/farmacocinéticaRESUMEN
Nifedipine is a dihydropyridine calcium channel blocker used widely in the management of hypertension and other cardiovascular disorders. In this work, a simple, rapid and sensitive liquid chromatography/tandem mass spectrometry method was developed and validated to determine nifedipine in dog plasma using nimodipine as the internal standard. Chromatographic separation was carried out on a C8 column. The mobile phase consisted of a mixture of acetonitrile, water and formic acid (60:40:0.2, v/v/v) at a flow rate of 0.5 mL/min. Detection was performed on a triple quadrupole tandem mass spectrometer in selected reaction monitoring mode via an atmospheric pressure chemical ionization source. The method has a lower limit of quantification of 0.20 ng/mL with consumption of plasma as low as 0.05 mL. The linear calibration curves were obtained in the concentration range of 0.20-50.0 ng/mL (r = 0.9948). The recoveries of the liquid extraction method were 74.5-84.1%. Intra-day and inter-day precisions were 4.1-8.8 and 6.7-7.4%, respectively. The quantification was not interfered with by other plasma components and the method was applied to determine nifedipine in plasma after a single oral administration of two controlled-release nifedipine tablets to beagle dogs.
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Cromatografía Líquida de Alta Presión/métodos , Nifedipino/sangre , Espectrometría de Masas en Tándem/métodos , Animales , Perros , Modelos Lineales , Masculino , Nifedipino/química , Nifedipino/farmacocinética , Reproducibilidad de los Resultados , Sensibilidad y EspecificidadRESUMEN
BACKGROUND: Selective motor control (SMC) is a fundamental component of typical human motion. As a result of brain damage, impaired SMC often leads to difficulties with coordination, balance, gait efficiency and symmetry. RESEARCH QUESTION: What is the association between impaired SMC and lower limb motor ability, functional balance and gait performance in children with bilateral spastic cerebral palsy (CP)? METHODS: Thirty-six children (aged 5-16 years) with spastic bilateral CP in Gross Motor Function Classification System (GMFCS) level I to II were included in this study. SMC was assessed using Selective Control Assessment of the Lower Extremity (SCALE). Gross motor function was assessed using Gross Motor Function Measure-88 items D and E dimension (GMFM-88 D&E). Functional balance was assessed using Pediatric Balance Scale (PBS) and Timed Up and Go Test (TUG). Gait quality was assessed using Edinburg Visual Gait Score (EVGS) and 10-Meter Walk Test (10MWT). Spearman's rank correlation analyses were used to determine the association between SMC and other factors. RESULTS: Correlation analyses showed that SCALE was strongly positively correlated with GMFM-88 (D&E) (rs=0.756, p < 0.001), PBS (rs=0.769, p < 0.001), and height-normalized fast walking speed (rs=0.632, p < 0.001), and strongly negatively correlated with TUG (rs=-0.766, p < 0.001) and EVGS (rs=-0.893, p < 0.001). SIGNIFICANCE: Lower extremity SMC deficits are associated with poor gross motor function and balance control, more severe overall gait deviations and decreased fast walking speed in children with bilateral spastic CP. Physical therapy should include interventions that promote selective motor control in order to improve overall functional ability.
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Parálisis Cerebral , Niño , Humanos , Equilibrio Postural , Espasticidad Muscular , Estudios de Tiempo y Movimiento , MarchaRESUMEN
Aesculetin (1) is an important coumarin found in various plant materials. It has been shown to have antiproliferative effects on several types of human cancer cells, but its effect on cervical cancer cells in vitro is unknown. In this study, we investigated that the cytotoxic effect of 1 on a non-cancer cell line (293) was smaller than on a tumor cell line (HeLa). This is the first report showing the possible mechanism of antiproliferative effect of 1 for the prevention of cervical cancer in cell culture models. It was found that 1 inhibited cell viability by inducing apoptosis, as evidenced by the formation of apoptotic bodies, generation of reactive oxygen species (ROS), and the accumulation of cells in the sub-G1 phase. Treatment with compound 1 decreased the cell growth in a dose-dependent manner with an IC(50) value of 37.8 microM. Aesculetin-induced apoptosis was correlated with mitochondrial dysfunction (DeltaPsi(m)), leading to the release of cytochrome c from the mitochondria to the cytosol, as well as the proteolytic activation of caspases in HeLa cells. These results indicate that 1 induces apoptosis in HeLa cells through a ROS-mediated mitochondrial dysfunction pathway.
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Antineoplásicos Fitogénicos/farmacología , Apoptosis/efectos de los fármacos , Mitocondrias/efectos de los fármacos , Umbeliferonas/farmacología , Antineoplásicos Fitogénicos/química , Bisbenzimidazol , Caspasas/efectos de los fármacos , Caspasas/metabolismo , Citocromos c/metabolismo , Ensayos de Selección de Medicamentos Antitumorales , Femenino , Células HeLa , Humanos , Mitocondrias/enzimología , Mitocondrias/fisiología , Modelos Biológicos , Estructura Molecular , Plantas Medicinales/química , Células Tumorales Cultivadas , Umbeliferonas/química , Neoplasias del Cuello UterinoRESUMEN
4alpha-Aminosteroids were synthesized by the substitution of a 2alpha-bromo ketone using K(2)CO(3) as an activator; 4beta-aminosteroids were synthesized in excellent yields by a highly regioselective and trans-stereospecific ring opening of a steroidal 3,4alpha-epoxide using ZnCl(2)-H(2)O as a catalyst.
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Androstanos/síntesis química , Esteroides/síntesis química , Androstanos/química , Catálisis , Cetonas/química , Esteroides/química , Zinc/químicaRESUMEN
Cremanthodium humile (C. humile) is a traditional herbal medicine for treatment of inflammation. Based on initial screening results, the purpose of this study was to evaluate the cytotoxic effect on four human cancer cell lines and one non-cancer cell line (293), then to determine the possible mechanisms of cell death elicited by the extract of C. humile on Hela cells. We have found the ether extract of C. humile (CH-EE) strongly decreased the survival rate of the four human tumor cell lines: Hela, A549, HepG2 and SW480. The cytotoxic effect of CH-EE on 293 was smaller than on tumor cell lines. Flow cytometry assays and nuclear staining showed that CH-EE induced apoptosis in Hela cells. This process was accompanied by the collapse of mitochondrial membrane potential, the release of cytochrome c and the activation of caspase-3/7 and -9. Furthermore, CH-EE generated reactive oxygen species (ROS) in Hela cells. These results indicate that CH-EE induces apoptosis in Hela cells through a ROS-mediated mitochondrial dysfunction pathway.
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Apoptosis/efectos de los fármacos , Asteraceae/química , Western Blotting , Caspasas/metabolismo , Ciclo Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Cromatografía Líquida de Alta Presión , Citocromos c/metabolismo , Dermatoglifia del ADN , Células HeLa , Humanos , Indicadores y Reactivos , Potenciales de la Membrana , Microscopía Fluorescente , Mitocondrias/efectos de los fármacos , Extractos Vegetales/farmacología , Especies Reactivas de Oxígeno/metabolismoRESUMEN
Three hydrazone ligands, H2L1-H2L3, made from salicylaldehyde and ibuprofen- or naproxen-derived hydrazides, were prepared and transformed into the corresponding copper(II) complexes [Cu(II)L1] x H2O, [Cu(II)L2], and [(Cu(II))2(L3)2] x H2O x DMF (Scheme). The X-ray crystal structure of the last-mentioned complex was solved (Fig. 1), showing a square-planar complexation geometry, and the single units were found to form a one-dimensional chain structure (Fig. 2). The interactions of these complexes with CT-DNA were studied by different techniques, indicating that they all bind to DNA by classical and/or non-classical intercalation modes.
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Aldehídos/química , Hidrazonas/química , Sustancias Intercalantes/química , Compuestos Organometálicos/química , Cobre/química , Cristalografía por Rayos X , ADN/química , Hidrazonas/síntesis química , Sustancias Intercalantes/síntesis química , Estructura Molecular , Compuestos Organometálicos/síntesis químicaRESUMEN
The microbial transformation of androst-4-ene-3,17-dione (I) by the fungus Beauveria bassiana CCTCC AF206001 has been investigated using pH 6.0 and 7.0 media. Two hydroxylated metabolites were obtained with the pH 6.0 medium. The major product was 11alpha-hydroxyandrost-4-ene-3,17-dione (II) whereas the minor product was 6beta,11alpha-dihydroxyandrost-4-ene-3,17-dione (III). On the other hand, four hydroxylated and/or reduced metabolites were obtained with the pH 7.0 medium. The major product was 11alpha,17beta-dihydroxyandrost-ene-3-one (V) and the minor products were 17beta-hydroxyandrost-ene-3-one (IV), 6beta,11alpha,17beta-trihydroxyandrost-ene-3-one (VI) and 3alpha,11alpha,17beta-trihydroxy-5alpha-androstane (VII). The products were purified by chromatographic methods, and were identified on the basis of spectroscopic methods. This fungus strain is clearly an efficient biocatalyst for 11alpha-hydroxylation and reduction of the 17-carbonyl group.
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Androstenodiona/metabolismo , Beauveria/metabolismo , Androstenodiona/química , Animales , Estructura MolecularRESUMEN
This paper addressed the application of hydroxyethyl pachyman (HEP) as a novel matrix for sustained - release tablets, using diclofenac sodium (DS) as a model drug. The studies showed the HEP tablets prepared by wet granulation had much slower drug release as compared to those prepared by direct compression. Meanwhile, increasing the percentage of HEP in the formulations caused a decrease in drug release rates. Moreover, DS release from the HEP tablets was much higher at high pH (6.8) than that at low pH (1.2). Morphology studies proved the HEP tablet formed a continuous gel layer with porous inner structure in the dissolution media. Analysis of DS release profiles revealed that diffusion and matrix erosion occurred in simulated intestinal fluid(SIF, pH=6.8) for all the tablets. The experimental results predict HEP has a potential as a hydrophilic matrix in tablets to prolong drug release.
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Excipientes/química , Glucanos/química , Antiinflamatorios no Esteroideos/química , Preparaciones de Acción Retardada/química , Diclofenaco/química , Liberación de Fármacos , Concentración de Iones de Hidrógeno , Interacciones Hidrofóbicas e Hidrofílicas , ComprimidosRESUMEN
Neuromuscular blocking agents are widely used as an anesthesia auxiliary in surgery, which induce relaxation of skeletal muscles by blocking signal transmission at the neuromuscular junction. Many neuromuscular blocking agents s were developed over the past decades, but none of them fully meets the needs of the clinic by various reasons. In this study, a series of quaternary ammonium steroidal neuromuscular blocking agents were synthesized and evaluated on isolated mouse phrenic nerve-hemidiaphragms for their bioactivities. The initial separation of mono- and bis-quaternary ammonium compounds turned out to be very challenging on regular silica gel chromatography. Therefore, a facile purification method, in which the silica gel was pretreated with methanolic sodium bromide solution, was finally achieved. Compounds 3g (0.36 µm) and 4g (0.37 µm) exhibited excellent neuromuscular blocking activities, which were about sixfold to sevenfold higher in potency than that of rocuronium (2.50 µm). In addition, other bis-quaternized compounds also showed good potencies close to that of rocuronium. Furthermore, the preliminary structure-activity relationship of this series was also elucidated. Benzyl group was found to be a promising quaternary group in this series.
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Compuestos de Amonio/farmacología , Bloqueantes Neuromusculares/farmacología , Esteroides/farmacología , Espectroscopía de Resonancia Magnética , Espectrometría de Masa por Ionización de ElectrosprayRESUMEN
Data communication and sharing of five level network of Public Health Information System, i.e. nation, province, district (city), county, and town, as far as to the countryside level were described, and how to apply the three solutions, i.e. Access VPN, Intranet VPN, and Extranet VPN of VPN technique to achieve the appropriation of the public network was also presented.
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Redes de Comunicación de Computadores/organización & administración , Informática en Salud Pública/métodos , Interfaz Usuario-Computador , China , HumanosRESUMEN
AIM: Nucleoside analogues have become the most promising candidates of anti-HBV drugs. In this study, beta-L-D4A was synthesized and explored its inhibitiory action against hepatitis B virus (HBV) in 2. 2. 15 cells derived from HepG2 cells transfected with HBV genome. METHODS: beta-L-D4A was stereo-controlled synthesized from D-glutamic acid, and the structure was identified by IR, 1H NMR and MS. 2. 2. 15 Cells were placed at a density of 5 x 10(4) per well in 12-well tissue culture plates, and treated with various concentrations of beta-L-D4A for 6 days. At the end, medium was processed to obtain virions by a polyethlene glycol precipitation method. At the same time, intracellular DNA was also extracted and digested with Hind III. Both of the above DNA were subjected to Southern blot, hybridized with a 32P-labeled HBV probe and autoradiographed. The intensity of the autoradiographic bands was quantitated by densitometric scans of computer and EC50 was calculated. 2. 2. 15 cells were also seeded in 24-well tissue culture plates, and cytotoxicity with different concentrations was examined by MTT method. IC50 was calculated. RESULTS: The synthesized compound structure conformed with beta-L-D4A; Autoradiographic bands showed similar for supernatant and intracellular HBV DNA. Episomal HBV DNA was inhibited in a dose-dependent manner. EC50 0.2 micromol x L(-1). The experiment of cytotoxicity gained IC50 200 micromol x L(-10. CONCLUSION: beta-L-D4A has been synthesized successfully. beta-L-D4A possessed potent inhibitory effect on replication of HBV in vitro with low cytotoxicity, TI value was 1 000. It is expected to be developed clinically into a new anti-HBV drug.
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Antivirales/síntesis química , Didesoxiadenosina/análogos & derivados , Virus de la Hepatitis B/efectos de los fármacos , Replicación Viral/efectos de los fármacos , Antivirales/química , Antivirales/farmacología , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Replicación del ADN/efectos de los fármacos , ADN Viral/efectos de los fármacos , Didesoxiadenosina/síntesis química , Didesoxiadenosina/química , Didesoxiadenosina/farmacología , Genoma Viral , Virus de la Hepatitis B/genética , Virus de la Hepatitis B/fisiología , Humanos , Neoplasias Hepáticas/patología , TransfecciónRESUMEN
BACKGROUND: A novel lovastatin (LVT)-loaded poly(lactic acid) microsphere suitable for oral administration was developed in this study, and in vitro and in vivo characteristics were evaluated. METHODS: The designed microspheres were obtained by an improved emulsion-solvent evaporation method. The morphological examination, particle size, encapsulation ratio, drug loading, and in vitro release were characterized. Pharmacokinetics studies were used to show that microspheres possess more advantages than the conventional formulations. RESULTS: By using the emulsion-solvent evaporation method, it was simple to prepare microspheres and easy to scale up production. The morphology of formed microspheres showed a spherical shape with a smooth surface, without any particle aggregation. Mean size of the microspheres was 2.65±0.69 µm; the encapsulation efficiency was 92.5%±3.6%, and drug loading was 16.7%±2.1%. In vitro release indicated that the LVT microspheres had a well-sustained release efficacy, and ex vivo studies showed that after LVT was loaded to microspheres, the area under the plasma concentration-time curve from zero to the last measurable plasma concentration point and the extrapolation to time infinity increased significantly, which represented 2.63-fold and 2.49-fold increases, respectively, compared to suspensions. The rate of ex vivo clearance was significantly reduced. CONCLUSION: This research proved that poly(lactic acid) microspheres can significantly prolong the drug circulation time in vivo and can also significantly increase the relative bioavailability of the drug.